Nervous Tissue Chapter 12 Overview of the Nervous System Cells of the Nervous System Electrophysiology of Neurons Synapses
Subdivisions of the Nervous System Two major anatomical subdivisions: Central Nervous System (CNS) the brain and spinal cord Peripheral Nervous System (PNS) nerves and ganglia outside of the CNS. (Ganglia are clusters of neurons)
Functional Divisions of PNS Sensory (Afferent) Division brings visceral (thoracic and abdominal organs) and somatic (skeletal muscle, skin, bone and joints) sensory information into the CNS Motor (Efferent) Division sends out information from the CNS. visceral motor division (Autonomic NS) innervates cardiac muscle, smooth muscle, glands sympathetic division (active, arousing responses) parasympathetic division (calming, maintenance functions like digestion) somatic motor division innervates skeletal muscle voluntary movement of skeletal muscles
Types of Neurons Sensory Neurons (afferent neurons) receptors that detect changes in the external environment and within the body (temperature, pressure, vibrations, light, chemicals) this information is transmitted into brain or spinal cord Interneurons (association neurons) positioned between sensory neurons and motor neurons in the CNS 90% of human neurons are interneurons interneurons process, store and retrieve information Motor Neurons (efferent neurons) send signals out to muscles and glands
Types of Neurons
Characteristics of Neurons Excitation (irritability) cells respond to changes in the body and external environment (the cells respond to stimuli) Conduction cells produce signals that travel from cell to cell Secretion when a signal reaches the end of an axon, a chemical neurotransmitter is released
Structure of a Neuron Cell Body (Soma) Axon Hillock Initial Segment Axon Dendrites Nissl (clumps of RER) Schwann Cells Nodes of Ranvier Terminal Arborization Terminal Bouttons
Dr. Franz Nissl (1860-1919) was born in Germany, he gravitated to medicine and as a student in Munich he wrote on pathology of cortical cells in which he used a stain he created which opened up a new era in neurocytology and neuropathology. Nissl Granules brought out by basic aniline stains perpetuate his name."but he also did outstanding work in psychiatry and demonstrated the correlation of nerves and mental disease by relating them to changes in glial cells, blood elements, blood vessels, and brain tissue in general. He worked with Alzheimer on general paresis. In the last 10 years of his life he did studies in which he established connections between the cortex and certain thalamic nuclei. http://www.uic.edu/depts/mcne/founders/page0067.html
Axon Hillock
Neurons and Glia immunofluorescent preparation
Neuron Morphologies Multipolar Neuron many dendrites one axon that may brach most common type of neuron Bipolar Neuron one dendrite one axon olfactory, retina, inner ear Unipolar Neuron only one process comes off soma also called pseudounipolar neurons sensory from skin and organs to spinal cord
Neuroglia Neuroglia are cells other than neurons in the nervous system (90% of cells in the CNS are glia, but they only account for 50% of the volume of the CNS). Many Schwann Cells cover each axon in the PNS. Each Oligodendrocyte covers parts of multiple axons in the CNS. Astrocytes most abundant glial cells - form framework of CNS form an important part of the blood-brain barrier by separating neurons from capillaries help regulate the composition of brain tissue intercellular fluid can produce action potentials like neurons Ependymal Cells form a ciliated simple columnar epithelium that lines cavities in the CNS and circulate cerebrospinal fluid (CSF). Microglia are bone marrow derived macrophages that move into the CNS and concentrate in areas of infection, trauma or stroke.
Neuroglia of the Central Nervous System
Ventricles of the Human Brain http://www.smartshunt.ethz.ch/project/formerproject/ventricles_color?hires
Myelin Sheath Myelin is formed by multiple wrappings of a glial cell membrane around an axon. Myelin is formed by oligodendrocytes in the CNS and by Schwann cells in the PNS. Myelination takes place during development of the nervous system. Wrappings of glial cell plasma membrane are about 20% protein and 80% lipid and make the axons look shiny white. Not all axons are myelinated, but all axons are covered by glial cells. Schwann cells hold short unmyelinated axons in grooves with only one membrane wrapping. Gaps between myelin segments are called Nodes of Ranvier these gaps are extremely small spaces where two myelin segments meet.
Myelin Sheath Formation Unmyelinated Axon Myelinated Axons
Node of Ranvier Myelin Sheath
Axons Schwann Cell Node of Ranvier
Electrical Potentials and Currents Nerve pathways are not continuous wires but a series of separate cells that relay signals. Neuronal communication is based on mechanisms for producing electrical potentials and currents. electrical potential - difference in concentration of charged ions across a membrane measured in millivolts (mv) electrical current - flow of ions across a membrane measured in milliamps (ma) Living cells have polarized membranes. Ions are maintained by the cell at different concentrations inside and outside of the cells. Membrane polarity of a resting (inactive) neuron is about - 70 mv because of a relatively negative charge inside of the cell compared to the outside of the cell.
Electrical potentials of living cells are measured using a sensitive voltmeter with tiny glass electrodes. One electrode is placed inside the cell (intracellular) and one electrode is placed just outside the cell (extracellular).
Neurophysiologists make extremely thin glass recording electrodes from glass tubes with instruments that precisely control the heat and tension on the tube. These hollow glass needles are then filled with a conducting salt solution. note: a sheet of paper is about 100 m thick!
Resting Membrane Potential (RMP) RMP is a voltage difference across the membrane of an inactive neuron and is usually about -70 mv. RMP is caused by: unequal ion distribution between Extracellular Fluid (ECF) and the Intracellular Fluid (ICF) caused by selective permeability of plasma membrane and active transport. Na + /K + pumps transport Na + and K + in a 3:2 ratio 3 Na + out of the neuron and 2 K + into the neuron pumps work continuously and require ATP high use of ATP means glucose and oxygen must be supplied continuously to nerve tissue large cytoplasmic anions do not escape (anionic proteins, PO 4 2-, SO 4 2- ) so inside of cell is negative.
Local Potentials Dendrite and soma membranes start to depolarize in a particular location when a neuron is stimulated by ligands (hormones or neurotransmitters from another cell), light, heat or a mechanical disturbance. membrane depolarizes due to opening of gated Na + channels that let Na + rush in according to its concentration and electrical gradients Local Potentials: are graded (vary in magnitude with stimulus strength) are decremental (get weaker the farther they spread) are reversible (as K + leaks out of cell and the Na + /K + pump works to restore membrane polarity) can lead to an action potential
Generation of a Local Membrane Potential
Summation of Depolarizations from Local Potentials can lead to an Action Potential Local depolarizing potentials are excitatory. Local potentials that bring the cell closer to threshold are called EPSPs (excitatory postsynaptic potentials). Depolarization must reach a threshold to trigger an action potential Local hyperpolarizing potentials would be inhibitory.
Synapse
Postsynaptic Potentials Excitatory postsynaptic potentials (EPSP) cause a positive voltage change in the postsynaptic cell making it more likely to fire (depolarize). result from Na + flowing into the cell noradrenaline and glutamate are excitatory neurotransmitters Inhibitory postsynaptic potentials (IPSP) cause a voltage change in the postsynaptic cell that makes it less likely to fire because it is hyperpolarized. results from Cl - flowing into the cell or K + leaving the cell glycine and GABA (gamma aminobutyric acid) are examples of inhibitory neurotransmitters Some neurotransmitters, like ACh and norepinephrine, can be either excitatory or inhibitory depending on the type of membrane receptor it binds to.
Excitatory (a) and Inhibitory (b) Postsynaptic Potentials
Summation of Postsynaptic Potentials Temporal Summation occurs when a single cell receives many EPSPs in a short period of time. Spatial Summation occurs when a single cell receives many EPSPs from more than one presynaptic cell.
Summation of EPSP s brings a cell to Threshold
Summation of IPSP s Inhibit Neurons synapse Inhibitory Neuron I suppresses presynaptic neuron S by releasing an inhibitory neurotransmitter like glycine. Inhibitory neurotransmitters can block voltage-gated calcium channels and open K + channels in neuron S dropping its membrane potential so it will not release neurotransmitter onto neuron R.
Action Potential Action Potential plotted on a realistic timescale looks like a spike. Initial depolarization events are very subtle and happen very quickly. Characteristics of an AP follows an all-or-none law voltage gates either open or they don t irreversible (once started, it goes to completion and can not be stopped)
Action Potential at the Axon Hillock 1. Sodium influx due to local potential spreads to the high density of voltage-gated channels at the trigger zone (500 channels/ m 2 at hillock vs 50 channels/ m 2 on soma). 2. If threshold potential (-55mV) is reached, voltage-gated Na + channels open (more Na + enters causing more depolarization). 3. Voltage-gated Na + channels open quickly. Incoming Na + further depolarizes membrane which opens more Na + channels (positive feedback). Voltage gated K + channels slowly start to open. 4. Depolarization peaks at+35mv
Action Potential at the Axon Hillock 4. Na + channels are inactivated and close above 0mV. Membrane is now positive on the inside. 5. Voltage-gated K + channels fully open, K + diffuses out. K + outflow and the Na + /K + pump repolarize the membrane. 6. K + channels stay open longer than Na + channels so more K + leaves the cell and the membrane voltage hyperpolarizes below the resting potential. 7. Ion diffusion through K + leak channels in the membrane or astrocyte scavenging of K + from the interstitial fluid restores resting membrane potential.
Membrane Potential (mv) Phases of the Action Potential Phases of the Action Potential 1 2 3 4 5 1 Time (milliseconds) TIME (msec) Phase 1 2 3 4 5 Name of Phase Resting Membrane Graded Local Potential Depolarization Repolarization Hyperpolarization Na + /K + pump Na + out K + in Na + out K + in Na + out K + in Na + out K + in Na + out K + in K + leak channels K + out K + out K + out K + out K + out voltage-gated Na + channel Closed and ready to open Closed and ready to open Open Closed and not able to open Closed and ready to open voltage-gated K + channel Closed Closed Slowly opening Open Slowly Closing Ion primarily responsible for the membrane voltage K + (out) Na + (in) Na + (in) K + (out) K + (out) membrane channel(s) primarily responsible for membrane voltage Na + /K + pump K + leak channels ligand-gated Na + channels voltage-gated Na + channels voltage-gated K + channels voltage-gated K + channels Na + /K + pump
voltage-gated
voltage-gated
voltage-gated
voltage-gated
Membrane Potential (mv) Depolarization Repolarization Hyperpolarization 0 Time (milliseconds)
Saladin Text page 460: A traveling nerve signal is an electrical current, but it is not the same as a current traveling through a wire. A current in a wire travels millions of meters per second and is decremental it gets weaker with distance. A nerve signal is much slower (not more than 2m/sec in unmyelinated fibers), but is nondecrimental. Even in the longest axons, the last action potential generated at a synaptic knob has the same voltage as the first one generated at the trigger zone. We can compare the nerve signal to a burning fuse. When a fuse is lit, the heat ignites powder immediately in front of this point and this repeats itself in a selfpropagating fashion until the end of the fuse is reached. At the end, the fuse burns just as hotly as it did at the beginning. In a fuse the combustible powder is the source of potential energy that keeps the process going in a nondecremental fashion. In an axon, the potential energy comes from the ion gradient across the plasma membrane. Thus, the signal does not grow weaker with distance; it is selfpropagating, like the burning of a fuse.
Burning Fuse http://www.youtube.com/watch?v=3odalbhr1zu Myth Busters outrunning a gunpowder trail 8:37-9:25 http://www.youtube.com/watch?v=b-iri1ba5jw&feature=related
The Refractory Period The Refractory Period is when a cell is resistant to stimulation. Assures one way conduction of the impulse because membrane channels are temporarily deactivated. No stimulus can start an action potential during the Absolute Refractory Period because the voltage-gated Na + channels are closed. Another action potential can be started by a stronger than normal stimulus because some voltage-gated Na + channels are reactivated.
The Refractory Period During the Refractory Period, voltage-gated Na + channels are inactivated by a protein tail that temporarily plugs the channel.
Impulse Conduction in Unmyelinated Fibers All healthy axons are covered by glial cells. Unmyelinated Axons are covered by a single layer of Schwann cell membrane (in the PNS) or oligodendrocyte membrane (in the CNS). Myelinated Axons are wrapped with many layers of glial cell membrane. Threshold voltage in the trigger zone (axon hillock) starts the impulse down the axon. Nerve signal (impulse) is a chain reaction of sequentially opening voltage-gated Na + channels down entire length of axon.
Impulse Conduction in Unmyelinated Fibers
Speed of Nerve Signals Signal speed depends on: diameter of the axon larger diameter = faster signal conduction because of increased membrane surface area for signal conduction myelination myelinated axons are faster because of saltatory conduction axons can be fast and thin (saves space) if they are myelinated Speeds: slow, unmyelinated fibers conduct at 0.5-2 m/sec (1-4 mph) slow pain fibers (burning, aching, throbbing pain) from a sprain, sun burn or stubbing a toe take a relatively long time to reach the CNS and last a long time. fast, myelinated fibers conduct at 120 m/sec (268 mph) fast pain fibers (sharp, pricking pain like stepping on a thorn) are conducted to the CNS quickly to help prevent further injury fast signals are also to skeletal muscles or from sensory organs for vision and balance
Saltatory Conduction in Myelinated Fibers Voltage-gated channels at Nodes of Ranvier fewer than 25 per m 2 in myelin-covered regions up to 12,000 per m 2 in nodes of Ranvier Fast Na + diffusion into axon occurs between nodes depolarizing the membrane and generating a local current flow that quickly spreads to the next node.
Saltatory Conduction in Myelinated Fiber The action potentials jump from node of Ranvier to node of Ranvier. (Saltator (L) a leaper, dancer)
Multiple Sclerosis Clinical Correlation Myelin sheaths formed by oligodendrocytes in the CNS deteriorate and are replaced by scar tissue. Deterioration may be caused by an immune disorder triggered by a virus in genetically susceptible individuals. Nerve conduction is disrupted. Specific symptoms depend upon the part of the CNS is involved. Symptoms can include double vision, blindness, speech defects, spontaneous muscle cramps, tremors, numbness.
Myelination and Brain Maturation Age 4 Age 8 Age 12 Age 16 Age 20 Few axons are covered with myelin at birth. More are insulated over time from the back of the cerebral cortex to the front. Basic functional areas such as vision (back) are completed before age 4, followed by language and last, self-control (forehead). Myelin is laid down until age 25 or so, one reason teenagers do not have adult decision- making abilities R. Douglas Fields Why White Matter Matters Scientific American, March 2008.
Synapses Between Neurons Neural Synapse: The specialized junction between the membranes of two neurons. 1st neuron is presynaptic neuron 2nd neuron is postsynaptic neuron First neuron affects the second neuron The first neuron releases a chemical called a neurotransmitter that will bind to a specific receptor on the second neuron. There are over 100 known neurotransmitters Synaptic delay = 0.5 milliseconds time for the signal to move from the presynaptic cell to the postsynaptic cell Synapse may be axodendritic, axosomatic or axoaxonic Number of synapses on postsynaptic cell is variable: 8,000 on spinal motor neuron 100,000 on some brain neurons like the Purkinje cell
Neuron Cytoplasm (red) Nucleus (purple) Synapses (green)
Synapse Between Neurons
Synaptic Vessicles containing Neurotransmitter Presynaptic Neuron Synaptic Cleft Postsynaptic Neuron
Types of Neurotransmitters There are over 100 different neurotransmitters, and these are classified in 4 major categories: 1. Acetylcholine (ACh) 2. Amino Acid Neurotransmitters GABA, glycine, aspartic acid 3. Biogenic Amines (Monoamines) Catecholamines: epinephrine, norepinephrine, dopamine Indolamines: serotonin, histamine 4. Neuropeptides (see next slide)
Neuropeptides Neuropeptides: are chains of 2-40 amino acids. are stored in synaptic vesicles in the terminal boutton. are powerful even at low concentrations. have long lasting effects. may also function as hormones if they are released into the blood.
Synaptic Transmission Two examples of synapses with different modes of action: Excitatory Adrenergic Synapse Inhibitory GABA-ergic Synapse
Excitatory Adrenergic Synapse Action potential opens voltage-gated Ca ++ channels on presynaptic neuron. Ca ++ influx triggers release of Norepinephrine (NE) into the synapse. NE works through a Second Messenger System. NE binds to receptors on the postsynaptic cell that starts a chemical cascade resulting in production of a second messenger, camp that can have multiple effects including activating enzymes, activating genes, and activating ligand-gated ion channels. NE is taken back up by the presynaptic neuron and recycled.
Excitatory Adrenergic Synapse
Inhibitory GABA-ergic Synapse Pre-synaptic neuron releases GABA ( -aminobutyric acid) into the synapse. GABA binds to receptors on the postsynaptic cell and triggers the opening of Cl - channels producing a hyperpolarization of the postsynaptic cell. Postsynaptic neuron is inhibited because it is now further away from threshold.